Antibiotic Resistance Threat: An Overview Of Changing Trends In 'Colistin' Use

Antibiotic Resistance Threat: An Overview Of Changing Trends In  'Colistin' Use

ATHIRA B.M

Antimicrobial resistance, a global problem, is particularly pressing in developing countries where the infectious disease burden is high and cost constrains the replacement of older antibiotics with newer, more expensive ones. Management of common and lethal bacterial infections has been critically compromised by the appearance and rapid spread of antibiotic-resistant bacteria. The bacterial disease burden in India is among the highest in the world; consequently, antibiotics will play a critical role in limiting morbidity and mortality in the country.

        The emergence of multidrug resistant (MDR) nosocomial pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, resistant to all currently available antibiotics, is coupled with the decline in the discovery and development of newer effective antibiotics over the last two decades. This has led to the depletion of most of the available therapeutic options for MDR bacterial infections.

        The antibiotic colistin is a prime example of increasing antimicrobial resistance (AMR). For many years it was rarely used on humans because of its harmful effects on the kidneys, although it has been used extensively in veterinary medicine. In recent years, however, colistin has again become a last-resort treatment for some patients with specific hard-to-treat bacterial infections. With the limited range of antimicrobials available to treat pan-resistant organisms, clinicians have become increasingly dependent on colistin, a polymyxin antibiotic discovered in 1949.

     Polymyxins are surface-acting ampipathic agents. Each polymyxin molecule has a cationic polypeptide ring with a lipophilic fatty acid side chain.The polypeptide ring binds with the anionic phosphate moieties in the bacterial cell membrane, displacing Ca 2+and Mg 2+, which are needed for membrane integrity. This results in increased permeability of the cell membrane causing leakage of cellular contents, leading to cell death. The disruption of membrane integrity also increases the susceptibility of the organism to hydrophilic antibiotics such as rifampicin, carbapenems, glycopeptides and tetracyclines, thus paving the way for both gram-negative and gram-positive antimicrobial synergistic combination therapy.

          Increasing antibiotic resistance and consequent increase in use of Colistin  is quite evident if we analyze the clinical practice in our hospital over last 3 years. When compared to previous years there is considerable increase in number of patients treated with Colistin in 2016 (Fig.1). In 2014 a total of 5 patients(0.0296%) were treated with Colistin, which became 16(0.0949%) in 2015 and 57(0.3382%) in 2016. All these patients were diagnosed with multi-drug resistant, colistin only sensitive infection. 

      Worryingly, and reflecting the decreasing efficacy of antibiotics in general, the effectiveness of colistin is now also diminishing. In November 2015, scientists announced the emergence of E. coli bacteria in China carrying the MCR-1 gene, which makes bacteria resistant to colistin. An infection with E. coli bacteria can cause gastroenteritis and even kidney failure. A study in The Lancet medical journal describes this as the ‘breach of the last group of antibiotics'.

   As hospitalized patients become more complex to treat, the increasing prevalence of antimicrobial resistance in both health care and community settings represents a daunting challenge. With the increasing complexity of infections and a paucity of new anti microbials in development, the future of successful antimicrobial therapy looks bleak. Antimicrobial stewardship can provide all practitioners with tools to prevent the overuse of valuable resources and help control the increase in antimicrobial resistance. The recognition of clinical pharmacists as key members of antibiotic stewardship teams in health systems is a milestone in infectious-diseases pharmacy practice. So its time for clinical pharmacists to take up the responsibility to assist in the war of antibiotic resistance.

References

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2.        Ramanan Laxminarayan, Ranjit Roy Chaudhury. Antibiotic Resistance in India: Drivers andOpportunities for Action. PLOS Medicine. 2016. 13(3); 1-7.

3.        Dr Nirmal K. Ganguly, Dr Sujith J. Chandy , Dr Mohamed Nadeem Fairoze et al. Rationalizing antibiotic use to limit antibiotic resistance in India. Indian J Med Res. 2011;134:  281-294.